This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Project 2, headed by Drs. Ruth Ruprecht and Frank Novembre, seeks to determine the level of polyclonal neutralizing antibodies needed to achieve protection against multiple low-dose challenges with simian-human immunodeficiency virus (SHIV) strains encoding R5-tropic envelope genes of recently transmitted HIV clade C (HIV-C). Polyclonal neutralizing antibodies were isolated from rhesus monkeys (RM) that had developed high-titer neutralizing antibodies during chronic SHIV infection. The antibodies were purified to only contain IgG;the resulting preparation is called SHIVIG. We have performed a passive immunization study to test the efficacy of SHIVIG against multiple low-dose challenges with SHIV-2873Nip, an R5 virus that is relatively difficult to neutralize (tier 2). We have tested three different doses of SHIVIG, and the challenges have been completed. Statistical analysis is ongoing.